Stem cell-based therapy is a novel approach to the treatment of neurological disorders. Such therapies involve the transplantation of neural stem cells, neural precursor cells, embryonic stem cells or adult stem cells, sometimes modified or pre-differentiated, into sites of neuronal injury or degeneration. Although precise mechanisms of action of stem cells transplanted to sites of injury are not known, the current view is that the beneficial effect of grafted stem cells on injured neural tissue derives either from replacement of endogenous cells, and/or secretion of neurotrophic factors, by the transplanted stem cells.
One concern associated with the use of embryonic stem cells for cell therapy is the possibility of oncogenic transformation of the grafted cells.
Another, universal problem associated with transplantation of stem cells into the brain, is the limited survival of grafted cells. For example, adult stem cells of mesenchymal origin (e.g., bone marrow, adipose tissue) have provided some promise for treatment of indications such as stroke, Parkinson's disease, and brain or spinal cord trauma; due to ease of their isolation, low immunogenicity, and low tendency toward oncogenic transformation. However, their typical engraftment rates are very low.
The poor long-term survival of bone marrow stem cells (BMSC) injected into the brain may be explained in part by their inability to adapt to microenvironments in the brain, which is atypical for mesenchymal cells, and may be unfavorable for their long-term growth and differentiation. Inflammation at a site of injury (due either to the initial neural trauma or to the transplantation procedure) could also be detrimental to the survival of engrafted cells.
The degree to which long-term survival of engrafted cells is important for repair of neural degeneration is unknown. However, the fact that beneficial effects are observed in cases in which survival of transplanted stem cells is very low implies the possible participation, in the repair process, of cellular products produced soon after transplantation, when injected cells are still alive. If this is the case, low survival of transplanted stem cells could result in decreased production of extracellular products that stimulate neural regeneration.
Because of the risk of oncogenic transformation associated with the use of embryonic stem cells, and the poor survival of adult stem cells, methods for treatment of neural disorders that take advantages of the unique properties of stem cells, and/or utilized unique extracellular products elaborated by stem cells, would have advantages over the use of stem cells themselves.